17 replies to this topic

[ozone]

I have a few questions for those scientific minds out there. As I've said in the past weeks, I've recently quit taking adderall. The most noticable effect of it was I could sit down and get my work done because I felt so motivated when I took it. I could sit for at times 6hrs straight with no problem. I've read up on it, and found that Adderall like all amphetamines, release more norepinephrine. Now quoting from Wikipedia...

Norepinephrine, known as noradrenaline outside the USA, is a catecholamine and a phenethylamine with chemical formula C8H11NO3. It is released from the adrenal glands as a hormone into the blood, but it is also a neurotransmitter in the nervous system where it is released from noradrenergic neurons during synaptic transmission. It is one of the 'stress hormones' and affects parts of the human brain where attention and impulsivity are controlled. Along with epinephrine this compound effects the fight-or-flight response, activating the sympathetic nervous system to directly increase heart rate, release energy from fat, and increase muscle readiness.

Changes in the norepinephrine system are implicated in depression. SNRIs treat depression by increasing the amount of serotonin and norepinephrine available to postsynaptic cells in the brain. There is some recent evidence that norepinephrine autoreceptors may also reuptake dopamine, implying SNRIs may increase dopamine transmission as well.

Also from what I've read, dopamine (not norepinephrine) is the controller of motivation and pleasure. But, when I was taking amphetamines I was feeling extremely focused and motivated. The Wikipedia info says that norepinephrine may indirectly affect dopamine... but how? I'm obviously guessing it does (otherwise why would they perscribe amphetamines for ADD) but most articles regarding amphetamines just say it releases norepinephrine and leaves it at that... so... what's the deal? Oh, and I'll also add that when I tried SAM-e I felt some motivation return (which scares me because that might mean that the motivation I'm lacking isn't ADHD related but rather depression related; even though I don't feel depressed [huh])

[johnmk]

I'm pretty sure SAM-e helps to increase levels of all neurotransmitters or it at least makes them all more efficient/potent. So I don't believe you can conclude you don't have ADHD. ADHD I like to think of as a gradient, everyone has it to some degree, like everyone has intelligence, a great or small amount of it. Of course the definition of disorder disagrees with me but I think we should relabel ADHD to something else to resolve that little problem.

[ozone]

@johnmk

Okay, I follow you there. But I'm still wondering about how increasing the amount of Norepinephrine affects dopamine.

[eudemon33]

Norepinepherin doesnt affect dopamine at all, rather dopamine affects Norepinepherin. You see its all part of a very complex process of creation and degredation of neurotransmitters.

Lemme give it to you in Lamens terms:

L-Phenylalanine(available OTC) becomes
L-Tyrosine(available OTC) which becomes
L-Dopa(available OTC) which becomes dopamine.
Now once the dopamine is no longer usefull to the neurons(ie: it has enough or has more coming) it sends out a chemical to break it down, thus becoming Norepinepherine. Not sure exactly how this process takes place, but it does.
Having lots of dopamine generally givees you lotsa' pleasure and energy, and Norepinepherine does the whole impulse/drive control thing.
So after all that shizzle happens, we get the NOR component of NORepinepherine chopped off in another breakdown process, and we get....can you guess? epinepherine!

Here are some synonyms for the two catechlomes: Norepinepherine is also Noradrenaline, and Epinepherine is also Adrenaline.

From my experience, you should try L-Tyrosine at 500-1000mg to achieve better focus, motivation, and drive.

Have fun!

[ozone]

Ah, nice. That's a good breakdown, although I have not read that dopamine is broken down into norepinephrine. But if that's true, thanks for the info. I already take L-Tyrosine but it just doesn't have that much of an affect on me. I ordered a NRI and should get it hopefully in a week. I'll tell ya how it works out.

Edited by ozone, 28 April 2005 - 02:35 AM.

[johnmk]

I wonder if there's an NRI or dopamine enhancing substance that doesn't boost anxiety at all. At above a certain dosage dextroamphetamine just causes me more anxiety and doesn't help with focus. A small amount of it however is just perfect.

[ozone]

I wonder if there's an NRI or dopamine enhancing substance that doesn't boost anxiety at all. At above a certain dosage dextroamphetamine just causes me more anxiety and doesn't help with focus. A small amount of it however is just perfect.

Well isn't dextroamphetamine a stimulant? Because I thought that only two (or thereabouts) NRIs exist which are non-stimulants: (1) Strattera; and (2) Reboxetine.

[johnmk]

I'm not exactly sure the distinction of non-stimulant vs. stimulant is so clear-cut. I think the terms are used as polar opposites too often when in fact the gradient is smooth and nothing is clear-cut. One should say one is more stimulating in a certain area of the body than the other, etc.

[ozone]

I'm not exactly sure the distinction of non-stimulant vs. stimulant is so clear-cut. I think the terms are used as polar opposites too often when in fact the gradient is smooth and nothing is clear-cut. One should say one is more stimulating in a certain area of the body than the other, etc.

If I really had to draw a distinction between the word "stimulant" and "non-stimulant" I guess it would be in the form of what an amphetamine versus a NRI does:

An amphetamine releases more norepinephrine, thus stimulating you.
A NRI prolongs the breakdown of existing norepinephrine, thus prolongong stimulation.

Again, just taking a stab at this, I can somewhat see why they say the former is addictive and the latter is not. Amphetamines make you feel a certain way, while NRI's just prolong you feeling a certain way. So if you don't feel a certain way to begin with, the NRI will do absolutely nothing for you. Is that clear cut? Not really imho, but I can at least see a distinction; and see arguably why a NRI may not be addictive.

[nuncle]

Just to clarify some of the claims made above:

The primary target of amphetamine and similar substances is the mesolimbic dopamine system. Certain classes of drugs may also exert an effect at norepinephrine synapses. That doesn't make them primarily norepinephrine drugs (unlike, say, Strattera). Virtually all major psychoactive compounds either (a) show affinity for more than one receptor type, or (b) affect multiple neurotransmitters via indirect cascades. So the claim that norepinephrine doesn't affect dopamine at all is inaccurate. There is a common synthesis pathway, yes, and in addition, the effects of these systems are intertwined in complex ways that are certainly not fully understood. It's impossible to increase the levels of one NT in a general fashion without altering the balance of plenty of others in the process.

This is generally a good point to keep in mind when evaluating many of the claims made in these (and other) forums. While it's ok to talk about the general roles the major neurotransmitters play, there are multiple (often dozens) of different subtypes of receptors for each neurotransmitter, numerous binding sites in the brain, and multiple functional roles a neurotransmitter can play. That's particularly true of the major transmitters (e.g., glutamate, GABA, etc.) which can have diametrically opposed functional roles depending on the particular system in question.

One nice example of how a failure to take complexity into account can have dramatical practical consequences (including for the kind of supplements you might want to take) is in the relationship of dopamine to attentional processes. It's been shown fairly reliably that there's an inverse U-shaped relationship between dopamine and attentional/working memory performance. I.e., being too low on DA leads to performance impairments, but so does being too high. What you want is to be somewhere in the optimal range--i.e., the middle. One way to get an intuitive sense of this is to think of the difference between the inability to sustain attention often associated with low basal DA levels, and the unpleasant 'overfocused' feeling some people get when taking stimulants (which increase DA levels). Indiscriminately increasing DA levels is certainly not guaranteed to improve cognitive performance, and in fact may substantially impair it if you're someone who's already naturally at the high end.

It's a safe bet that these kinds of trade-offs characterize most neurotransmitter systems. In general, one should be wary of vague claims that substances 'increase levels of transmitter X in the brain'. Even when true, there's no guarantee that it's always a good thing to increase such levels, an assumption that seems to be implicit in many of the recommendations made on these forums.

[ozone]

@nuncle
Point taken. I don't claim to know much about this topic at all; I'm just trying to learn more each day.
This was a really good read comparing the difference between the effects of a NRI versus an Amphetamine: http://www.psychiatr...orms/br6402.pdf.

[ozone]

I was reading some more on NRIs and I find the concept fascinating. The info I read said the reason NRI's work is because in the frontal part of our brain we have many norepinephrine reuptake-receptors, and very few dopamine reuptake-receptors. Well, the nifty thing about reuptake-receptors is that they share - i.e., a norepinephrine receptor can also reuptake dopamine. So in the brain when dopamine is released, in the frontal part of the brain all the dopamine is sucked back up via the norepinephrine receptors before the majority of it can be used by the brain. So, by blocking the norepinephrine receptor, it thus blocks reuptake of dopamine through the norepinephrine receptors. And as I said before, because of the limited number of dopamine receptors in the frontal part of the brain, the dopamine will actually have a good chance at being fully utilized now. Pretty cool.

[triguy]

l-dopa is OTC?


mucuna the dopa bean?

L-Phenylalanine(available OTC) becomes
L-Tyrosine(available OTC) which becomes
L-Dopa(available OTC) which becomes dopamine

I have taken mucuna and have never reallly felt dopamine "effects"

What would you guys suggest if one feels better on higher dopamine levels?

[johnmk]

Maybe a bit of deprenyl. Nicotine patch as well, perhaps. Careful not to break any laws in your country however, many addictions arise out of that particular neurotransmitter system, it is thought, which is why substances substantially affecting dopamine are tightly regulated. If you feel you have any particular disorders, you may wish to see a psychiatrist or a neurologist for substances that can have a powerful rectifying effect.

[triguy]

thanx john,

I have used GHB in the past with no problems & never understood how people got addicted. I appreciate your concern. I will report on the deprenyl & nicotene patch, i am working with a psych

[power.bulls.x]

i have tried reboxetine (Edronax) in small dosage.
what i can say is this the shit:
i make my heart speed up.
And i can sit for like 3h-4hours and get boring things/stuff done.
It makes me so f**king determined!
I realy love that stuff more efficient than deprenyl for lack of motivation .

How safe is thta stuff ?
is it a real nootropic that lacks of serious sides like pirac/hydergine/deprenyl/... ?

So far it reduced my sleep time to 5hours witch might not be healthy ?

[goku]

I'd like to hear more from nuncle. He's right. Neurotransmitter knowledge by even the most prominent in the field is still pretty primitive.

[goku]

And has that relentless improvement add at the top of every page gotten larger lately, or is it just me?